{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:19:14Z","timestamp":1784229554234,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Council of Thailand (NRCT) and Chulalongkorn University","award":["N42A680085"],"award-info":[{"award-number":["N42A680085"]}]},{"name":"Second Century Fund (C2F), Chulalongkorn University","award":["N42A680085"],"award-info":[{"award-number":["N42A680085"]}]},{"name":"the Faculty of Pharmaceutical Sciences, Chulalongkorn University","award":["N42A680085"],"award-info":[{"award-number":["N42A680085"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Natural phytochemicals from Dendrobium species, particularly bibenzyl derivatives, possess diverse pharmacological activities, yet their potential against GBM remains largely unexplored. Here, we investigated the anticancer activity of 4,5,4\u2032-trihydroxy-3,3\u2032-dimethoxybibenzyl (TDB), a potent antioxidant bibenzyl derivative isolated from Dendrobium pachyglossum. In U87MG cells, TDB reduced viability in a dose- and time-dependent manner, suppressed clonogenic growth, induced apoptosis via Bax upregulation and Bcl-xL\/Mcl-1 downregulation, and inhibited both mTORC1 and mTORC2 signaling. TDB also impaired cell migration and downregulated epithelial\u2013mesenchymal transition (EMT)-associated proteins. Notably, TDB enhanced the cytotoxicity of temozolomide (TMZ), the current standard of care for GBM. These TMZ-sensitizing properties were further confirmed in patient-derived xenograft (PDX) Jx22 cells. To assess its potential for central nervous system delivery, blood\u2013brain barrier (BBB) permeability was predicted using four independent in silico platforms\u2014ADMETlab 3.0, LogBB_Pred, LightBBB, and BBB Predictor (Tree2C)\u2014all of which consistently classified TDB as BBB-permeable. This predicted CNS accessibility, together with its potent anticancer profile, underscores TDB\u2019s translational promise. Collectively, our findings identify TDB as a plant-derived antioxidant with multifaceted anti-GBM activity and favorable BBB penetration potential, warranting further in vivo validation and preclinical development as a novel therapeutic candidate for GBM.<\/jats:p>","DOI":"10.3390\/antiox14101212","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T12:46:56Z","timestamp":1759841216000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Bibenzyl from Dendrobium pachyglossum Exhibits Potent Anti-Cancer Activity Against Glioblastoma Multiforme"],"prefix":"10.3390","volume":"14","author":[{"given":"Hnin Mon","family":"Aung","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onsurang","family":"Wattanathamsan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittipong","family":"Sanookpan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aphinan","family":"Hongprasit","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5422-1023","authenticated-orcid":false,"given":"Chawanphat","family":"Muangnoi","sequence":"additional","affiliation":[{"name":"Biological Science and Animal Model Unit, Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianthong","family":"Phumsuay","sequence":"additional","affiliation":[{"name":"Biological Science and Animal Model Unit, Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanawan","family":"Rojpitikul","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-4122","authenticated-orcid":false,"given":"Boonchoo","family":"Sritularak","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Natural Products for Ageing and Chronic Diseases, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tankun","family":"Bunlue","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3946-1798","authenticated-orcid":false,"given":"Naphat","family":"Chantaravisoot","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Systems Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia R.","family":"Oliva","sequence":"additional","affiliation":[{"name":"Free Radical & Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne E.","family":"Griguer","sequence":"additional","affiliation":[{"name":"Free Radical & Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3582-5980","authenticated-orcid":false,"given":"Visarut","family":"Buranasudja","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Natural Products for Ageing and Chronic Diseases, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. 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